Effects of Sterol Structure on Insect Herbivore Physiology, Biochemistry and Molecular Biology

Sterols serve two important biological functions in animals - they act as cellular membrane components, and as the precursor to steroid hormones. Insects require a dietary source of sterol because they cannot synthesize sterols de novo. Cholesterol is the most common sterol in plant-feeding insects, but because plants contain very little cholesterol, plant-feeding insects must convert plant sterols into cholesterol. In this dissertation I investigate the effect of common and novel plant sterols and steroids found in a transgenic tobacco line on several caterpillar species. I also explore the metabolism of these sterols and steroids, and use a microarray approach to identify genes involved in sterol use and metabolism in plant-feeding insects. I also study cholesterol homeostasis using a grasshopper species. Modified tobacco plants containing a novel sterol profile negatively affected performance three different caterpillar species, especially in the second generation. Insects reared on modified plants contained less total sterols and cholesterol than those on control plants having normal sterol profile. Similar results were found using artificial diets containing atypical steroids, e.g., cholestanol and cholestan-3-one, identified in the tobacco plants that were fed to my experimental caterpillars. More importantly, the sterol/steroid ratio, but not their absolute amount in the diets, determined the negative effects. Caterpillar species could convert stigmasterol, a common plant sterol, into cholesterol. They could also convert cholestan-3-one into cholestanol and epicholestanol, although this ability varied among different species. A microarray study, that focused on gene expression in midgut tissue, indicated that stigmasterol, cholestanol and cholestan-3-one could induce different gene expression level, and that cholestan-3-one caused a the largest pool of genes to be regulated. The genes possibly involved in the metabolism of stigmasterol and cholestan-3-one were reported. These findings are important in directing further research on the potential application of plant sterol modification to control pests in agricultural systems. Insect herbivores could behaviorally regulate the intake of several nutrients, but they could not regulate their sterol intake. They did, however, practice cholesterol homeostasis, by postingestively regulating tissue sterol levels, even when feeding on diets with high cholesterol content. Collectively, the results from this dissertation provide unique insight into cholesterol regulation, which is difficult to achieve in mammals that are capable of synthesizing their own sterols

Equilibrium Financing in a Distribution Channel with Capital Constraint

There exist capital constraints in many distribution channels. We examine a channel consisting of one manufacturer and one retailer, where the retailer is capital constrained. The retailer may fund its business by borrowing credit either from a competitive bank market or from the manufacturer, provided the latter is willing to lend. When only one credit type (either bank or trade credit) is viable, we show that trade credit financing generally charges a higher wholesale price and thus becomes less attractive than bank credit financing for the retailer. When both bank and trade credits are viable, the unique equilibrium is trade credit financing if production cost is relatively low but is bank credit financing otherwise. We also study the case where both the retailer and the manufacturer are capital constrained and demonstrate that, to improve the overall supply chain efficiency, the bank should finance the manufacturer if production cost is low but finance the retailer otherwise. Our analysis further suggests that the equilibrium region of trade credit financing shrinks as demand variability or the retailer\u27s internal capital level increases

The Cash Flow Advantages of 3PLs as Supply Chain Orchestrators

With an increasingly open global economy and advanced technologies, some third-party logistics providers (3PLs), such as Eternal Asia, have emerged as supply chain orchestrators, linking buyers with manufacturers worldwide. In addition to their traditional transportation services, these orchestrators provide procurement and financial assistance to buyers in the supply network, especially small- and medium-sized enterprises (SMEs) in developing countries. Oftentimes, the 3PLs can obtain payment delay arrangements from the financially stronger manufacturers, which in turn can be partially extended to the SME buyers, alleviating their high costs of capital. To illustrate the efficiency improvements of the aforementioned practice, we use a model to explicitly capture the cash-flow dynamics in a supply chain consisting of a manufacturer, a buyer, and a 3PL firm and explore the conditions under which this innovation benefits all parties in the supply chain so that the business model is sustainable. We characterize these conditions and show that the supply chain profit can be higher under leadership by the 3PL than by the manufacturer. The intermediary role of the 3PL is crucial, in that its benefit may vanish if the manufacturer chooses to directly grant payment delay to the buyers. We demonstrate that the benefit is more likely to occur with more buyers. We further identify the unique Nash bargaining solution for the transportation time and the payment delay grace period

A review of factors influencing sensitive skin: an emphasis on built environment characteristics

BackgroundSensitive skin (SS) is a condition characterized by hyperreactivity. Impacting around 37 percent of the worldwide population and exerting an influence on the quality of life for affected individuals. Its prevalence rate has increased due to factors such as elevating stress levels and deteriorating environmental conditions. The exposome factors influencing SS have extended from demographic, biological attributes, and lifestyle to external environments. Built environments (BEs) have demonstrated as root drivers for changes in behaviors and environmental exposure which have the potential to trigger SS, but the review of the associations between BEs and SS is currently lacking.ObjectiveThis review aims to achieve two primary objectives: (1) Examine exposome factors that exert influence on SS at the individual and environmental levels. (2) Develop a theoretical framework that establishes a connection between BEs and SS, thereby offering valuable insights into the impact of the built environment on this condition.MethodsAn extensive literature search was carried out across multiple fields, including sociology, epidemiology, basic medicine, clinical medicine, and environmental research, with a focus on SS. To identify pertinent references, renowned databases such as PubMed, Web of Science, and CNKI were utilized.ResultsSS is the outcome of interactions between individual attributes and environmental factors. These influencing factors can be categorized into five distinct classes: (1) demographic and socioeconomic characteristics including age, gender, and race; (2) physiological and biological attributes such as emotional changes, skin types, sleep disorders, and menstrual cycles in women; (3) behavioral factors, such as spicy diet, cosmetic use, alcohol consumption, and physical exercise; (4) natural environmental features, including climate conditions and air pollution; (5) built environmental features such as population density, green space availability, road network density, and access to public transportation, also have the potential to affect the condition.ConclusionThe importance of interdisciplinary integration lies in its ability to ascertain whether and how BEs are impacting SS. By elucidating the role of BEs in conjunction with other factors in the onset of SS, we can provide guidance for future research endeavors and the formulation of interventions aimed at mitigating the prevalence of SS

Possible Luttinger liquid behavior of edge transport in monolayer transition metal dichalcogenide crystals.

In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics

Boosting the performance of single-atom catalysts via external electric field polarization

Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal “onsite electrostatic polarization” mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk